新生儿坏死性小肠结肠炎肠道微生物群研究进展
Research Progress on Intestinal Microbiota in Neonatal Necrotizing Enterocolitis
DOI: 10.12677/acm.2025.154901, PDF,   
作者: 曹 涵, 韦 红*：重庆医科大学附属儿童医院新生儿科，儿童发育疾病研究教育部重点实验室，国家儿童健康与疾病临床医学研究中心，重庆
关键词: 新生儿坏死性小肠结肠炎；微生物；病理生理学；Neonatal Necrotizing Enterocolitis； Microbes； Pathophysiology
摘要: 新生儿坏死性小肠结肠炎(NEC)是新生儿的一种严重的胃肠道疾病，是新生儿尤其是早产儿死亡和残疾的重要原因。NEC的发病机制尚不完全明确，目前研究认为该疾病是在易感宿主的基础上通过饮食和细菌等因素发展而来的。随着NEC的进展，肠穿孔可导致严重感染，肠道微生物易位进入血液循环，可导致严重的败血症和死亡。这篇综述讲述了NEC与肠道微生物之间的相互作用，主要探讨了NEC的病理生理学、肠道微生物群的作用以及潜在的预防治疗策略。
Abstract: Neonatal necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in newborns and represents a leading cause of mortality and disability, particularly in preterm infants. The pathogenesis of NEC remains incompletely understood, though current evidence suggests that the disease develops in predisposed hosts in response to dietary and bacterial factors. As NEC progresses, intestinal perforation may lead to severe infection, while microbial translocation into the bloodstream can result in life-threatening sepsis and death. This review explores the intricate interplay among NEC and the gut microbiota, with a focus on elucidating the pathophysiology of NEC, the role of gut microbial dysbiosis, and potential preventive and therapeutic strategies.
文章引用：曹涵, 韦红. 新生儿坏死性小肠结肠炎肠道微生物群研究进展[J]. 临床医学进展, 2025, 15(4): 51-57. https://doi.org/10.12677/acm.2025.154901

参考文献

[1] Niño, D.F., Sodhi, C.P. and Hackam, D.J. (2016) Necrotizing Enterocolitis: New Insights into Pathogenesis and Mechanisms. Nature Reviews Gastroenterology & Hepatology, 13, 590-600. [Google Scholar] [CrossRef] [PubMed]
[2] Hull, M.A., Fisher, J.G., Gutierrez, I.M., Jones, B.A., Kang, K.H., Kenny, M., et al. (2014) Mortality and Management of Surgical Necrotizing Enterocolitis in Very Low Birth Weight Neonates: A Prospective Cohort Study. Journal of the American College of Surgeons, 218, 1148-1155. [Google Scholar] [CrossRef] [PubMed]
[3] Pammi, M., Cope, J., Tarr, P.I., Warner, B.B., Morrow, A.L., Mai, V., et al. (2017) Intestinal Dysbiosis in Preterm Infants Preceding Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis. Microbiome, 5, Article No. 31. [Google Scholar] [CrossRef] [PubMed]
[4] Garg, P.M., Paschal, J.L., Ansari, M.A.Y., Block, D., Inagaki, K. and Weitkamp, J. (2022) Clinical Impact of Nec-Associated Sepsis on Outcomes in Preterm Infants. Pediatric Research, 92, 1705-1715. [Google Scholar] [CrossRef] [PubMed]
[5] Parra-Llorca, A., Pinilla-Gonzlez, A., Torrejón-Rodríguez, L., Lara-Cantón, I., Kuligowski, J., Collado, M.C., et al. (2023) Effects of Sepsis on Immune Response, Microbiome and Oxidative Metabolism in Preterm Infants. Children, 10, Article 602. [Google Scholar] [CrossRef] [PubMed]
[6] Bizzarro, M.J., Ehrenkranz, R.A. and Gallagher, P.G. (2014) Concurrent Bloodstream Infections in Infants with Necrotizing Enterocolitis. The Journal of Pediatrics, 164, 61-66. [Google Scholar] [CrossRef] [PubMed]
[7] Martinez-Tallo, E., Claure, N. and Bancalari, E. (1997) Necrotizing Enterocolitis in Full-Term or Near-Term Infants: Risk Factors. Neonatology, 71, 292-298. [Google Scholar] [CrossRef] [PubMed]
[8] Andrews, R.E. and Coe, K.L. (2021) Clinical Presentation and Multifactorial Pathogenesis of Necrotizing Enterocolitis in the Preterm Infant. Advances in Neonatal Care, 21, 349-355. [Google Scholar] [CrossRef] [PubMed]
[9] Patel, R.M., Ferguson, J., McElroy, S.J., Khashu, M. and Caplan, M.S. (2020) Defining Necrotizing Enterocolitis: Current Difficulties and Future Opportunities. Pediatric Research, 88, 10-15. [Google Scholar] [CrossRef] [PubMed]
[10] Sampah, M.E.S. and Hackam, D.J. (2021) Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders. Frontiers in Immunology, 12, Article 650709. [Google Scholar] [CrossRef] [PubMed]
[11] Perez-Muñoz, M.E., Arrieta, M., Ramer-Tait, A.E. and Walter, J. (2017) A Critical Assessment of the “Sterile Womb” and “in Utero Colonization” Hypotheses: Implications for Research on the Pioneer Infant Microbiome. Microbiome, 5, Article No. 48. [Google Scholar] [CrossRef] [PubMed]
[12] Costello, E.K., Carlisle, E.M., Bik, E.M., Morowitz, M.J. and Relman, D.A. (2013) Microbiome Assembly across Multiple Body Sites in Low-Birthweight Infants. mBio, 4, e00782-13. [Google Scholar] [CrossRef] [PubMed]
[13] Afrazi, A., Branca, M.F., Sodhi, C.P., Good, M., Yamaguchi, Y., Egan, C.E., et al. (2014) Toll-Like Receptor 4-Mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis. Journal of Biological Chemistry, 289, 9584-9599. [Google Scholar] [CrossRef] [PubMed]
[14] Sodhi, C.P., Shi, X., Richardson, W.M., Grant, Z.S., Shapiro, R.A., Prindle, T., et al. (2010) Toll-Like Receptor-4 Inhibits Enterocyte Proliferation via Impaired β-Catenin Signaling in Necrotizing Enterocolitis. Gastroenterology, 138, 185-196. [Google Scholar] [CrossRef] [PubMed]
[15] Hackam, D.J. and Sodhi, C.P. (2018) Toll-Like Receptor-Mediated Intestinal Inflammatory Imbalance in the Pathogenesis of Necrotizing Enterocolitis. Cellular and Molecular Gastroenterology and Hepatology, 6, 229-238.e1. [Google Scholar] [CrossRef] [PubMed]
[16] Masi, A.C. and Stewart, C.J. (2019) The Role of the Preterm Intestinal Microbiome in Sepsis and Necrotising Enterocolitis. Early Human Development, 138, Article ID: 104854. [Google Scholar] [CrossRef] [PubMed]
[17] Rodríguez, J.M., Murphy, K., Stanton, C., Ross, R.P., Kober, O.I., Juge, N., et al. (2015) The Composition of the Gut Microbiota Throughout Life, with an Emphasis on Early Life. Microbial Ecology in Health & Disease, 26, Article ID: 26050. [Google Scholar] [CrossRef] [PubMed]
[18] Stewart, C.J., Embleton, N.D., Marrs, E.C.L., Smith, D.P., Fofanova, T., Nelson, A., et al. (2017) Longitudinal Development of the Gut Microbiome and Metabolome in Preterm Neonates with Late Onset Sepsis and Healthy Controls. Microbiome, 5, Article No. 75. [Google Scholar] [CrossRef] [PubMed]
[19] Zheng, D., Liwinski, T. and Elinav, E. (2020) Interaction between Microbiota and Immunity in Health and Disease. Cell Research, 30, 492-506. [Google Scholar] [CrossRef] [PubMed]
[20] Fan, Y. and Pedersen, O. (2020) Gut Microbiota in Human Metabolic Health and Disease. Nature Reviews Microbiology, 19, 55-71. [Google Scholar] [CrossRef] [PubMed]
[21] Levy, M., Kolodziejczyk, A.A., Thaiss, C.A. and Elinav, E. (2017) Dysbiosis and the Immune System. Nature Reviews Immunology, 17, 219-232. [Google Scholar] [CrossRef] [PubMed]
[22] Thänert, R., Keen, E.C., Dantas, G., Warner, B.B. and Tarr, P.I. (2020) Necrotizing Enterocolitis and the Microbiome: Current Status and Future Directions. The Journal of Infectious Diseases, 223, S257-S263. [Google Scholar] [CrossRef] [PubMed]
[23] Claud, E.C., Keegan, K.P., Brulc, J.M., Lu, L., Bartels, D., Glass, E., et al. (2013) Bacterial Community Structure and Functional Contributions to Emergence of Health or Necrotizing Enterocolitis in Preterm Infants. Microbiome, 1, Article No. 20. [Google Scholar] [CrossRef] [PubMed]
[24] Mai, V., Torrazza, R.M., Ukhanova, M., Wang, X., Sun, Y., Li, N., et al. (2013) Distortions in Development of Intestinal Microbiota Associated with Late Onset Sepsis in Preterm Infants. PLOS ONE, 8, e52876. [Google Scholar] [CrossRef] [PubMed]
[25] Taft, D.H., Ambalavanan, N., Schibler, K.R., Yu, Z., Newburg, D.S., Deshmukh, H., et al. (2015) Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants. PLOS ONE, 10, e0130604. [Google Scholar] [CrossRef] [PubMed]
[26] Yazji, I., Sodhi, C.P., Lee, E.K., Good, M., Egan, C.E., Afrazi, A., et al. (2013) Endothelial TLR4 Activation Impairs Intestinal Microcirculatory Perfusion in Necrotizing Enterocolitis via Enos-No-Nitrite Signaling. Proceedings of the National Academy of Sciences, 110, 9451-9456. [Google Scholar] [CrossRef] [PubMed]
[27] Good, M., Siggers, R.H., Sodhi, C.P., Afrazi, A., Alkhudari, F., Egan, C.E., et al. (2012) Amniotic Fluid Inhibits Toll-Like Receptor 4 Signaling in the Fetal and Neonatal Intestinal Epithelium. Proceedings of the National Academy of Sciences of the United States of America, 109, 11330-11335. [Google Scholar] [CrossRef] [PubMed]
[28] Sodhi, C.P., Wipf, P., Yamaguchi, Y., Fulton, W.B., Kovler, M., Niño, D.F., et al. (2020) The Human Milk Oligosaccharides 2’-Fucosyllactose and 6’-Sialyllactose Protect against the Development of Necrotizing Enterocolitis by Inhibiting Toll-Like Receptor 4 Signaling. Pediatric Research, 89, 91-101. [Google Scholar] [CrossRef] [PubMed]
[29] Xu, G., Davis, J.C., Goonatilleke, E., Smilowitz, J.T., German, J.B. and Lebrilla, C.B. (2017) Absolute Quantitation of Human Milk Oligosaccharides Reveals Phenotypic Variations during Lactation. The Journal of Nutrition, 147, 117-124. [Google Scholar] [CrossRef] [PubMed]
[30] Wang, C., Zhang, M., Guo, H., Yan, J., Liu, F., Chen, J., et al. (2019) Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Inhibiting Intestinal Damage via Increasing the Proliferation of Crypt Cells. Molecular Nutrition & Food Research, 63, Article ID: 1900262. [Google Scholar] [CrossRef] [PubMed]
[31] Morgan, R.L., Preidis, G.A., Kashyap, P.C., Weizman, A.V., Sadeghirad, B., Chang, Y., et al. (2020) Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-Analysis of Randomized Trials. Gastroenterology, 159, 467-480. [Google Scholar] [CrossRef] [PubMed]
[32] Underwood, M.A. (2019) Probiotics and the Prevention of Necrotizing Enterocolitis. Journal of Pediatric Surgery, 54, 405-412. [Google Scholar] [CrossRef] [PubMed]
[33] Good, M., Sodhi, C.P., Ozolek, J.A., Buck, R.H., Goehring, K.C., Thomas, D.L., et al. (2014) lactobacillus Rhamnosus HN001 Decreases the Severity of Necrotizing Enterocolitis in Neonatal Mice and Preterm Piglets: Evidence in Mice for a Role of TLR9. American Journal of Physiology-Gastrointestinal and Liver Physiology, 306, G1021-G1032. [Google Scholar] [CrossRef] [PubMed]
[34] Bury, R.G., Tudehope, D. and Cochrane Neonatal Group (1996) Enteral Antibiotics for Preventing Necrotizing Enterocolitis in Low Birthweight or Preterm Infants. Cochrane Database of Systematic Reviews, No. 1, CD000405.
[35] Ting, J.Y., Roberts, A., Sherlock, R., Ojah, C., Cieslak, Z., Dunn, M., et al. (2019) Duration of Initial Empirical Antibiotic Therapy and Outcomes in Very Low Birth Weight Infants. Pediatrics, 143, e20182286. [Google Scholar] [CrossRef] [PubMed]
[36] Shah, D. and Sinn, J.K. (2012) Antibiotic Regimens for the Empirical Treatment of Newborn Infants with Necrotising Enterocolitis. Cochrane Database of Systematic Reviews, No. 8, CD007448. [Google Scholar] [CrossRef] [PubMed]

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